Angiogenesis in diabetes and obesity

Abstract

The prevalence of diabetes mellitus and obesity continues to increase globally. Diabetic vascular complications are the main chronic diabetic complications and associated with mortality and disability. Angiogenesis is a key pathological characteristic of diabetic microvascular complications. However, there are two tissue-specific paradoxical changes in the angiogenesis in diabetic microvascular complications: an excessive uncontrolled formation of premature blood vessels in some tissues, such as the retina, and a deficiency in the formation of small blood vessels in peripheral tissues, such as the skin. This review will discuss the paradoxical phenomena of angiogenesis and its underlying mechanism in obesity, diabetes and diabetic complications.

Fig. 1

The disturbed angiogenic balance in impaired wound healing in diabetes and diabetic retinopathy. Diabetic retinopathy is the result of over-production of angiogenic stimulators and reduced angiogenic inhibitors in the retina; impaired wound healing in diabetes is the consequence of elevated systemic levels of angiogenic inhibitor and reduced angiogenic stimulator levels. VEGF vascular endothelial growth factors; EPO erythropoietin; WNT the wingless-type MMTV integration site; PEDF pigment epitheliumderived factor; TSP-1 thrombospondin-1.

Fig. 2

Signaling pathways in the regulation of VEGF transcription. Signaling pathways, related transcription factors of VEGF and the corresponding response elements in the VEGF promoter are summarized. Sp1 specific protein-1; Stat3 signal transducer and activator of transcription-3; HIF-1 hypoxia-inducible factor-1; AP-1 activator protein-1; AP-2 activator protein-2; NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells; TGF-β transforming growth factor beta; MAPK Mitogenactivated protein kinases; NO Nitric oxide; EGF Epidermal growth factor; PDGF Platelet-derived growth factor; IL-6 Interleukin 6; WNT the wingless-type MMTV integration site; TCF T-cell factor.